Autonomic Pharm & Kinetics Flashcards
On the log enzyme kinetics graph, y-intercept is equal to?
1/Vmax
The lower the Km,
the _____ the affinity.
higher
On the log kinetics graph:
Competitive inhibitors cross each other competitively.
T/F
T
They all cross on 1/Vmax
On the log kinetics graph:
Noncompetitive inhibitors do not cross each other.
T/F
T
they have different Km’s
Vd = ?
amt of drug in body /
plasma drug concentration
t1/2 = ?
0.7 * Vd / clearanc
A drug infused at a constant rate reaches about 94% of steady state after x half-lives?
x = 4
Loading dose = ?
Cp * Vd/F
Cp = target plasma conc. F = bioavailability: =1 per IV
Phase 1 metabolism involves?
yields?
reduction, oxidation, hydrolysis
cytochrome P450
yields slightly polar, still-active water-soluble metabolites
Geriatrics lost this first
Phase 2 metabolism involves?
yields?
acetylation, glucuronidation, sulfation, conjugation
yields very polar, inactive metabolites
Potency = ? Efficacy = ?
Potency = amt needed for a given effect
Efficacy = maximal effect
Therapeutic index =
TD50 /
ED50
(median toxic dose /
median effective dose)
Skeletal Muscle.
N or M?
neurotransmitter?
N
ACh
PNS: Cardiac & Smooth Muscle, gland cells.
N or M?
neurotransmitter?
N——-M (2 neurons)
Ach Ach
All sympathetic @ ganglion.
N or M?
neurotransmitter?
N
ACh
Sympathetic 2nd neuron @ sweat glands:
N or M?
neurotransmitter?
M
ACh
Sympathetic @ cardiac and smooth muscle, gland cells, nerve terminals
neurotransmitter?
NE @ alpha or beta
Sympathetic at Renal vascular smooth muscle
receptor??
D1
Sympathetic @ adrenal medulla
N or M?
neurotransmitter?
N, ACh
G-protein-linked 2nd messengers:
a1 ->
G-prot class?
functions?
q
Inc’d vascular smooth muscle contraction
G-protein-linked 2nd messengers:
a2
i Dec'd sympathetic outflow Dec'd insulin release Dec'd lipolysis Inc'd platelet aggregation
G-protein-linked 2nd messengers:
B1
s Inc'd HR, Inc'd contactility Inc'd renin release Inc'd lipolysis
G-protein-linked 2nd messengers:
B2
s vasodilation, bronchodilation Inc'd HR, contractility, lipolysis, insulin release, aqueous humor production Dec'd uterine tone (tocolysis) Ciliary muscle relaxation
G-protein-linked 2nd messengers:
M1
q
CNS
G-protein-linked 2nd messengers:
M2
i
Dec’d HR & contractility of atria
G-protein-linked 2nd messengers:
M3
q
Inc’d exocrine gland secretions, gut peristalsis, bladder contraction, bronchoconstriction, pupillary sphincter muscle (miosis) & ciliary muscle contraction (accommodation)
G-protein-linked 2nd messengers:
D1
s
relaxes renal vascular smooth muscle
G-protein-linked 2nd messengers:
D2
i
modulates transmitter release, esp in brain
G-protein-linked 2nd messengers:
H1
q Inc'd nasal/bronchial mucus bronchconstriction pruritis pain
G-protein-linked 2nd messengers:
H2
s
Inc’d gastic acid secretion
G-protein-linked 2nd messengers:
V1
contracts vascular smooth muscle
G-protein-linked 2nd messengers:
V2
Inc’d H20 permeability & reabsorption in the collective tubules
H1, a1, V1, M1, M3
G-prot class?
cell signals?
Gq — Phoslipase C — PIP2 — DAG & IP3…
IP3 — inc Ca (smooth muscle contraction
DAG — PKC
B1, B2, D1, H2, V2
G-prot class?
cell signals?
Gs — adenylcyclase — (converts ATP into cAMP)…
cAMP — PKA — 2 actions:
- inc’d Ca(2+) in heart
- inhibits myosin light chain kinase (smooth muscle)
M2, a2, D2
Gi (inhibits) —X adenylcyclase — (converts ATP into cAMP)…
cAMP — PKA — 2 actions:
- inc’d Ca(2+) in heart
- inhibits myosin light chain kinase (smooth muscle)
Guanethidine
decreases NE release
Metyrosine
decreases DOPA formation from tyrosine
Reserpine
inhibits DA uptake into secretory vesicles; inhibiting its release @ nerve junction
Hemicholinium?
Vesamicol?
H: inhibits presynaptic choline reuptake
V: inhibits ACh loading into secretory vesicles
Bethanechol
clin?
action?
cholinomimetic direct agonist
clin: postop & neurogenic ileus & urinary retention
action: activates Bowel & Bladder smooth muscle; resistant to AChE
Carbachol
clin?
action?
Cholinomimetic direct agonist
clin: glaucoma, pupillary contraction, & release of intraocular pressure
act: contracts ciliary muscle of eye (open angle), pupillar sphincter (narrow angle); resistant to AChE
Pilocarpine
cholinomimetic direct agonist
potent stimulator of sweat, tears, saliva
Methacholine
cholinomimetic direct agonist
challenge test for dx of asthma
stimulates muscarinic receptors
Neostigmine
cholinomimetic indirect agonist
clin: postop & neurogenic ileus & urinary retention, myasthenia gravis, reversal of nueromuscular junction blockade(postop)
act: inc’d endogenous ACh; no CNS penetration
Pyridostigmine
cholinomimetic indirect agonist
myasthenia gravis, increases strength
act: inc’d endogenous ACh; no CNS penetrance
Edrophonium
cholinomimetic indirect agonist
dx of Myasthenia G (extremely short acting)
act: inc’d endogenous ACh;
Physostigmine
cholinomimetic indirect agonist
glaucoma (crosses BBB to CNS) and atropine OD
act: inc’d endogenous ACh;
Echothiophate
cholinomimetic indirect agonist
glaucoma
act: inc’d endogenous ACh;
Cholinesterase inhibitor poisoning symptoms:
antidote?
DUMBBELSS
Diarrhea Urination Miosis Bronchospasm Bradycardia Excitation of skeletal muscle and CNS Lacrimation Sweating Salivation (also abd cramps)
ANTIDOTE: atropine (muscarinic antagonist) plus pralidoxime (chemical antagonist used to regenerate active cholinsterase)
homatropine
tropicamide
atropine
Muscarinic antagonist (eye)
produces mydriasis & cycloplegia
Benztropine
Muscarinic antagonist (CNS)
parkinson’s dz (2nd line)
Scopolamine
Muscarinic antagonist (CNS)
motion sickness
Ipratropium, Tiotropium
Muscarinic antagonist (respiratory)
Asthma, COPD
Oxybutynin, Glycopyrrolate
O: Muscarinic antagonist (genitourinary)
Reduces urgency in mild cystitis and reduces bladder spasms
G: Muscarinic antagonist (GI, respiratory)
Parenteral: pre-op to reduce airway secretions
Oral: drooling, peptic ulcer
Glaucoma
brimonide
mech?
tox?
mech: alpha agonist
_aqueous humor synth
SE: no pupillary or vision changes
Glaucoma
betaxolol, timolol, carteolol
mech?
tox?
mech: beta-blocker
_aqueous humor secretion
SE: no pupillary or vision changes
Glaucoma
Acetazolamide
mech?
tox?
mech: diuretic
_aqueous humor secretion via inhibition of carbonic anydrase
SE: no pupillary or vision changes
Glaucoma
pilocarpine, carbachol, physostigmine, echothiophate
mech?
tox?
mech: cholinomimetic
_outflow of aqueous humor; contracts ciliary muscle –>
opens trabecular meshwork
use pilocarpine in emergencies as it is very effetive at opening canal of Schlemm
SE: miosis, cyclospasm
Glaucoma
Latanoprost
mech?
tox?
mech: prostaglandin
_outflow of aqueous humor;
tox: darkens color of iris (browning)
ATROPINE
uses?
Muscarinic antagonist
EYE: _pupil dilation, cycloplegia AIRWAY: _secretions Stomach: _acid secretion Gut: _motility Bladder: _urgency in cystitis
BLOCKS SLUD: Salivation Lacrimation Urination Defecation
ATROPINE
tox?
TOX:
_body temp; rapid pulse; dry mouth; dry, flushed skin; cycloplegia; constipation; disorientation
can cause acute angle-closure glaucoma in elderly, urinary retention in men w/prostatic hypertrophy, and hyperthermia in infants
Hot as a…
Hot as a hare Dry as a bone, red as a beet, blind as a bat mad as a hatter
Hexamethonium
mech: nicotinic ACh receptor antagonist
clin: ganglionic blocker. Used in exp models to prevent vagal reflexz response to changes in BP–e.g. prevents reflex bradycardia caused by NE
Sympathomimetic selectivity
Epi
__ __ __ __
low doses selective for __
uses: anaphylaxis, glaucoma(open angle), asthma, hypoTN
Sympathomimetic selectivity
NE
__ __ > __
_SBP, DBP –> reflex bradycardia
clin:
hypoTN(but _renal perfusion)
Sympathomimetic selectivity
Iso
__=__ > __ __
_SBP, DBP
_HR
clin: AV block (rare)
Sympathomimetic selectivity
Dopa
D1=D2 > __ __ > __ __
clin:
shock(increases renal perfusion), HF
Sympathomimetic selectivity
Dobu
__ __ __ __
Phenoxybenzamine (irrev)
phentolamine (rev)
nonsel. _-blocker
clin: pheochromocytoma
tox: orthostatic HTN
reflex tachycardia
Prazosin, terazosin, doxazosin
__ selective
clin: HTN, BPH
tox: 1st dose orthoHTN, dizziness, headache
Mirtazapine
__ selective
clin: depression
tox: sedation, _serum chol, _appetite
olol’s
clin & tox?
Beta-blockers HTN: _CO, _renin secretion Angina: _HR/contractility, resulting in _O2 use MI: _mortality SVT: _AV conduction velocity CHF: slows progression of CHF Glaucoma (timolol): _aq humor secretion
TOX: impotence, exacerabtion of asthma, CV adverse effects, CNS adverse effects
olol’s
non selective & selective(A BEAM of b1 blockers)?
nonselective: propranolol, timolol, nadolol, pindolol (partial agonist), labetalol (partial agonist)
Beta1 selective: Acetbutolol (partial), betaxolol, Esmolol (short acting), Atenolol, Metroprolol
